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Polyester amide polymers (PEA) were evaluated for <jats:italic>in vitro<\/jats:italic> cytotoxicity and <jats:italic>in vivo<\/jats:italic> biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine model predisposed to IVD degeneration at long\u2010term (6 months) follow\u2010up. PEA extracts did not induce cytotoxicity in mouse fibroblast cells (microscopy and XTT assay), while a slight foreign body reaction was demonstrated by histopathology after intramuscular implantation in rabbits. Intradiscal injection of a volume of 40 \u00b5L through 26 and 27G needles induced no degenerative changes in acanine model susceptible to IVD disease. Although sham\u2010injected IVDs showed increased <jats:italic>CAV1<\/jats:italic> expression compared with noninjected IVDs, which may indicate increased cell senescence, these findings were not supported by immunohistochemistry, biomolecular analysis of genes related to apoptosis, biochemical and histopathological results. PEAM\u2010injected IVDs showed significantly higher <jats:italic>BAX\/BCL2<\/jats:italic> ratio vs sham\u2010injected IVDs suggestive of an anti\u2010apoptotic effect of the PEAMs. These findings were not supported by other analyses (clinical signs, disc height index, T2 values, biomolecular and biochemical analyses, and IVD histopathology). PEAs showed a good cytocompatibility and biocompatibility. PEAMs are considered safe sustained release systems for intradiscal delivery of biological treatments. \u00a9 2015 The Authors. <jats:italic>Journal of Biomedical Materials Research Part B: Applied Biomaterials<\/jats:italic> published by Wiley Periodicals, Inc. 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